Efficacy of Medications Approved for the Treatment of Alcohol Dependence and Alcohol Withdrawal Syndrome in Female Patients: A Descriptive Review.

The aim of this study was to evaluate whether the number of women recruited for studies to establish the efficacy of medications approved for treatment of alcohol dependence (AD) and of alcohol withdrawal syndrome (AWS) is sufficient to reveal possible gender differences in the response to these medications and in suggesting the use of different doses in female patients. Our results show that the rates of women recruited for studies evaluating the efficacy of disulfiram (1%), benzodiazepines (3%), and anticonvulsants (13%) were too low to establish possible gender differences. The rates of women recruited for studies evaluating the efficacy of acamprosate (22%), naltrexone (23%), and nalmefene (30%) were higher and allowed evaluation of data obtained for female patients. Women receive medications for treatment of AD and/or AWS for which efficacy has been demonstrated in studies in which men were more largely represented.

Dexmedetomidine for Alcohol Withdrawal Syndrome.

OBJECTIVE: To review available evidence evaluating dexmedetomidine in alcohol withdrawal syndrome (AWS) while identifying gaps in evidence for its use in this setting. DATA SOURCES: A MEDLINE search (1966-August 2015) to identify English-language articles evaluating the efficacy and safety of dexmedetomidine in alcohol withdrawal. Key words included alcohol, withdrawal, delirium tremens, and dexmedetomidine. Additional references were identified from a review of literature citations. STUDY SELECTION AND DATA EXTRACTION: All English-language observational studies, retrospective reviews, and clinical trials were included. Case reports and case series describing the use of dexmedetomidine in 10 or fewer patients were excluded. DATA SYNTHESIS: One randomized, controlled trial, 1 prospective observational study, and 6 retrospective reviews were identified. The only randomized, controlled trial identified showed that the addition of dexmedetomidine decreases benzodiazepine requirements more than placebo in the first 24 hours after initiation compared with the 24 hours prior to initiation (-56.8 mg vs -8 mg; P = 0.037). Overall, dexmedetomidine appears to lower benzodiazepine requirements in patients with AWS and decreases the sympathomimetic response seen in these patients. There was no convincing evidence that dexmedetomidine improves clinical endpoints in patients with AWS, such as need for mechanical ventilation or intensive care unit or hospital length of stay. CONCLUSIONS: Dexmedetomidine reduces hypertension and tachycardia in AWS and also reduces benzodiazepine requirements; however, the impact of these findings on important clinical endpoints is yet to be determined. Dexmedetomidine may be useful as adjunctive therapy; however, it cannot be recommended as a single agent in the management of AWS.

Review of adjunctive dexmedetomidine in the management of severe acute alcohol withdrawal syndrome.

BACKGROUND: The primary management of alcohol withdrawal involves the administration of a γ-aminobutyric acid agonist, such as benzodiazepines, for management of symptoms and to prevent further progression to seizure or delirium tremens. Despite escalating doses of benzodiazepines, published literature indicates that some patient's alcohol withdrawal syndrome symptoms do not respond, and that the use of adjunctive agents may be beneficial in these patients. Dexmedetomidine, an α2-agonist, serves as a potential adjunctive agent through management of associated autonomic symptoms. Understanding of recent literature evaluating its use is necessary for appropriate selection. OBJECTIVE: To review available literature supporting the use of adjunctive dexmedetomidine for management of severe alcohol withdrawal syndrome. METHODS: A total of 13 published articles evaluating the efficacy and safety of dexmedetomidine as an adjunctive agent for the treatment of alcohol withdrawal in adult patients were identified from a MEDLINE search using the key words alcohol withdrawal, delirium tremens and dexmedetomidine. RESULTS: Evaluation of the literature indicates that dexmedetomidine is associated with a decrease in short-term benzodiazepine requirements after initiation, and improvement in hemodynamic parameters in relation to the adrenergic drive present in alcohol withdrawal. CONCLUSION: The use of dexmedetomidine in the management of severe alcohol withdrawal should be considered as an adjunctive agent. Dexmedetomidine appears to be well tolerated, with an expected decrease in blood pressure and heart rate. Seizures have occurred in patients with alcohol withdrawal despite the use of dexmedetomidine, with and without benzodiazepines, due to lack of γ-aminobutyric acid agonist administration.

Successful treatment of severe alcohol withdrawal delirium with very high-dose diazepam (260-480 mg) administration.

INTRODUCTION: Alcohol withdrawal delirium, commonly known as "delirium tremens (DT)", is the most severe clinical condition of alcohol withdrawal syndrome (AWS). Symptoms of DT include changes in consciousness and cognitive and perceptual impairments that fluctuate during the day. Treatment includes general support, such as helping the patient to re-orientate, close monitoring of vital signs and adequate hydration, and symptomatic treatment for agitation, autonomic instability, and hallucinations. In symptomatic treatment of DT, benzodiazepines are most commonly preferred due to their GABA-ergic effects. Diazepam, a benzodiazepine, has a faster onset of action than other benzodiazepines when administered intravenously (iv) and effectively controls symptoms. Although low doses of diazepam usually relieve DT symptoms, very high doses may be required in some patients. This case series discusses patients receiving high doses of diazepam to relieve DT symptoms. CASE REPORT: Four male patients aged from 43 to 57 years who regularly consumed alcohol with a daily average of 20-100 standard drinks and developed DT afterwards and were followed up in the intensive care unit are presented. In these patients, the symptoms of DT were relieved, and somnolence was achieved with the administration of very high-dose IV diazepam (260-480 mg/day), contrary to routine treatment doses. All patients were successfully treated and discharged without any morbidity. CONCLUSION: Severe AWS can potentially result in death otherwise managed quickly and adequately. Diazepam is a suitable agent for severe AWS or DT treatment. Clinicians should keep in mind that high-dose diazepam treatment may be required in the treatment of DT that develops after a long-term and high amount of alcohol consumption. Publications reporting the need for very high doses of diazepam in DT are limited and usually published long ago; in this context, our findings are significant. The evidence is often based on case reports and uncontrolled studies, so controlled trials are needed to determine optimal treatment doses in severe DT.

An innovative inpatient protocol for alcohol withdrawal prevention in a 16-year-old adolescent: a case report.

BACKGROUND: Alcohol cessation in youth with daily drinking poses a risk of severe and life-threatening alcohol withdrawal. If unsupervised, alcohol withdrawal in heavy users can cause severe complications, such as seizures, delirium tremens, and death. We present the case of a teenager admitted at our pediatric center for the prevention of alcohol withdrawal using an innovative protocol, including a fixed-dosage benzodiazepine regimen. CASE DESCRIPTION: A 16-year-old Caucasian male, known to have anxiety and an attention deficit disorder, was electively admitted for medical stabilization and surveillance of alcohol withdrawal. He had been previously diagnosed with alcohol use disorder and had a past history of withdrawal symptoms. He was prescribed a course of thiamine, folic acid, as well as a fixed-dosage benzodiazepine taper over 5 days. His withdrawal symptoms were evaluated using a standardized Clinical Institute Withdrawal Assessment for Alcohol scale. During his stay, he reported minimal symptoms, as well as a score on the Clinical Institute Withdrawal Assessment for Alcohol scale consistently lower than 5. His mood, motivation, eating habits and sleeping patterns significantly improved during his stay. He developed no medical complications and demonstrated pride in his successes. He was successfully transferred to a long-term rehabilitation center. CONCLUSIONS: A withdrawal prevention protocol was developed on the basis of existing literature. It included a soothing environment, basic laboratory work evaluating the medical complications of alcohol use, as well as medication aiming to prevent and reduce potential withdrawal symptoms. The patient responded well to the fixed-dosage taper with minimal symptoms and discomfort. Although alcohol use in adolescents is frequent, alcohol withdrawal in this population is rarely seen in a pediatric hospital setting. Nonetheless, given the lack of existing guidelines regarding alcohol withdrawal in adolescents, standardized protocols could be greatly beneficial for the prevention of this condition in this population.

An alcohol withdrawal tool for use in hospitals.

An estimated 40% of patients admitted with alcohol-related problems to Glasgow hospitals are at risk of alcohol withdrawal syndrome (AWS). Not managing them effectively can affect the physical and psychological wellbeing of staff and other patients. This article describes the development and implementation of a tool, the Glasgow Modified Alcohol Withdrawal Scale, to manage patients with AWS. It is part of a more comprehensive assessment and management protocol and incorporates a protocol to help nurses decide whether to administer fixed-dose or symptom-triggered benzodiazepine to these patients.

[Acute benzodiazepine withdrawal delirium].

In this case report we describe a life-threatening episode of delirium in a 51-year-old man. The condition was triggered by an abrupt withdrawal of benzodiazepines. The patient had been taking multiple sedatives for several years but a large proportion of the drugs were not available in Denmark. His general practitioner substituted and prescribed oxazepam and zolpidem for ten days. Afterwards the patient did not have access to benzodiazepines and developed a severe benzodiazepine withdrawal delirium. He was treated with diazepam and olanzapine with gradual dose reduction.

Alcohol withdrawal syndrome: symptom-triggered versus fixed-schedule treatment in an outpatient setting.

AIMS: To investigate whether, in the treatment with chlordiazepoxide for outpatient alcohol withdrawal, there are advantages of symptom-triggered self-medication over a fixed-schedule regimen. METHODS: A randomized controlled trial in outpatient clinics for people suffering from alcohol dependence (AD) and alcohol-related problems; 165 adult patients in an outpatient setting in a specialized alcohol treatment unit were randomized 1:1 to either a symptom-triggered self-medication or tapered dose, using chlordiazepoxide. Alcohol withdrawal symptoms, amount of medication, duration of symptoms, time to relapse and patient satisfaction were measured. Patients assessed their symptoms using the Short Alcohol Withdrawal Scale (SAWS). Patient satisfaction was monitored by the Diabetes Treatment Satisfaction Questionnaire. We used the Well-Being Index and the European addiction severity index for the 1-year follow-up. RESULTS: We found no differences in the quantity of medication consumed, time to relapse, well being or treatment satisfaction. CONCLUSION: Symptom-triggered self-medication was as safe as fixed-schedule medication in treating outpatients with AD and mild to moderate symptoms of AWS. The SAWS is a powerful monitoring tool, because it is brief and permits the subject to log the withdrawal symptoms.

Delirium tremens in an AUD patient after an intrathecal baclofen pump induced total alcohol abstinence.

OBJECTIVE: Delirium Tremens (DT) is the most severe complication of alcohol withdrawal syndrome (AWS), and has a mortality rate of 1-5%. Baclofen is recommended for spasticity treatment, but it has recently been used for alcohol withdrawal symptoms reduction and alcohol abstinence. CASE REPORT: A cervical spinal cord injury patient was treated for two years with oral baclofen 80 mg/day for spasticity. He is alcohol-dependent and a cannabis user and required an intrathecal baclofen (ITB) pump implant. A week after the implant, he stopped drinking, as "he didn't felt the urge anymore". The AWS appeared five days after the last alcohol intake and DT at 7 days. Diazepam 20 mg was used up to three times per day, but didn't seem to improve or reduce the anxiety, agitation, visual or auditory hallucinations. Two years later the patient remains alcohol abstinent and still on intrathecal baclofen. CONCLUSIONS: Alcohol-dependent patients can abruptly stop their alcohol intake, while in continuous infusion of intrathecal baclofen. Baclofen can be useful in the acute treatment of AWS as it seems to reduce diazepam requirements and in long-term alcohol abstinence. In the presence of AWS, while on chronic baclofen, no dose reduction should be attempted, as it can worsen the AWS or trigger baclofen withdrawal.

[Alcohol hallucinosis]. / Alcoholhallucinose.

BACKGROUND: Alcohol hallucinosis is a rare complication of chronic alcohol abuse characterized by the acute onset of hallucinations during or after an episode of alcohol use. The hallucinations may persist for a long time, due to which the clinical picture can be mistaken for a disorder on the schizophrenia spectrum. The prognosis tends to be favourable, although untreated cases are associated with a considerable mortality risk (37% in eight years). CASE DESCRIPTION: A 38-year-old male was admitted to a psychiatric hospital with hallucinations of acute onset during alcohol abuse which persisted for two months of abstinence. The patient experienced visual, auditory and tactile hallucinations during which time his consciousness, attention, orientation and higher cognitive functions remained intact. Somatic and neuroimaging investigations showed no abnormalities. The patient partially recovered on treatment with haloperidol. CONCLUSION: If hallucinations are experienced during or after a period of alcohol abuse, the diagnosis of alcohol hallucinosis should be considered. The diagnosis must be distinguished from delirium tremens and schizophrenia spectrum disorder as treatment and prognosis are essentially different.

Alcohol prescription by surgeons in the prevention and treatment of delirium tremens: historic and current practice.

Beer, other alcohol beverages, and IV alcohol are still used to prevent or treat alcohol withdrawal delirium on surgical services. The history of the use of alcohol by surgeons may play a role in its continued use for withdrawal. In this policy survey 32 inpatient hospital pharmacies were called and asked if alcohol was available, if it was used to treat alcohol withdrawal, and the medical specialties that requested it. Recommendations about the use of alcohol were examined in recent textbooks and from those published early in the twentieth century. One half of the 32 hospitals surveyed had alcoholic beverages available for patient use and eleven hospitals used either package alcohol or IV alcohol in the treatment of alcohol withdrawal. Surgeons used alcohol before anesthesia to help patients tolerate procedures, and the use of alcohol for treatment of alcohol withdrawal still appears in the surgical literature. This preliminary survey indicates that some hospitals still provide beverage alcohol for the treatment of alcohol withdrawal and that surgeons are the specialty ordering alcohol for their patients.

[Atrium-related hepatitis. Report of four cases]. / Hépatites au cours de l'administration d'Atrium. Observation de quatre cas.

Four patients developed acute hepatitis after receiving Atrium, an association of phenobarbital, febarbamate and difebarbomate, for the treatment of tremor or for the prevention of alcohol withdrawal symptoms. Hepatitis occurred 1 to 3 months after treatment. Asthenia was the unique clinical manifestation. Marked increase in serum aminotransferases and gamma-glutamyltranspeptidase levels were the main biological features. Histological examination showed liver cell necrosis in two cases, prominent in the centrolobular area in one case. There was no case of hepatic failure. Atrium withdrawal was followed by complete recovery within 6 to 12 weeks. The mechanism of Atrium hepatotoxicity remains unknown.

[Adjuvant therapy with parenteral piracetam in alcohol withdrawal delirium]. / Piracetam infúziós alkalmazása adjuváns kezelésként alkoholmegvonásos delirium kezelésében.

The author reports his results of parenteral piracetam treatment in 193 patients admitted to the Psychiatric Department of Semmelweis Hospital with alcohol withdrawal delirium. Alcohol withdrawal delirium is a complex metabolic disorder, the disturbance of the highest cerebral integrative functions, which is caused by the impairment of cerebral oxidative metabolism. Piracetam is effective on most neurotransmitter systems, without a specific receptor agonism or antagonism, increases the effectivity of different biogenic amine systems, has also an effect on membrane permeability, increases the concentration of NMDA (methyl-D-aspartate) receptors in the impaired brain and improves cognitive functions. In the patients suffered from alcohol dependence piracetam produces positive morphologic changes, by decreasing lipofuscin accumulation. In early stage it prevents the development of delirium. Despite of the great number (approximately 150) of medication that were tried in the treatment of delirium, the ideal one still has not been found. Among the accessible therapeutic possibilities the author searched for methods which make the treatment more effective. The administration of parental piracetam, therefore was brought into his therapeutical protocol. Parenteral piracetam--similarly to literature data--proved to be effective in the treatment of alcohol withdrawal delirium. Considering the present--insufficient--hospital financing, it is remarkable that though the costs of the new therapy are higher than the traditional meprobamat therapy, through less side effect it is more economical (overall costs lower) and by decreasing the time of delirium it is more humane to the patients.

[Alcohol withdrawal syndrome and delirium tremens. Diagnosis and therapy]. / Alkoholentzugssyndrom und Delirium tremens. Diagnose und Therapie.

The alcohol withdrawal syndrome can be classified into three degrees of severity on the basis of the symptomatology, autonomic withdrawal, predelirium and delirium tremens. In American literature the severity of withdrawal is recorded using the CIWA-A scale (Clinical Institute Withdrawal Assessment--Alcohol). The pathophysiological causes lie in an imbalance between the inhibitory and excitatory neurotransmitters after giving up alcohol. This results in predomination by the excitatory system. Therapeutic intervention is possible here. Clomethiazole has effective sedative actions, stabilises the autonomic nervous system, and is an anticonvulsant. It is the drug of choice for autonomic withdrawal and predelirium. The benzodlazepines have a similar effect, but cannot be controlled so accurately. Carbamazepine can prevent withdrawal convulsions and progression of delirium. Clonidine acts on autonomic withdrawal and, together with neuroleptics and benzodiazepines, is easy to use parenterally for delirium tremens, while parenteral clomethiazole harbours dangers.